11-3029392-G-A

Position:

chr11-3029392-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001014437.3(CARS1):c.853C>T(p.Leu285Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00929 in 1,614,076 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 77 hom. )

Consequence

CARS1
NM_001014437.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.911

Variant links:

Genes affected

CARS1 (HGNC:1493): (cysteinyl-tRNA synthetase 1) This gene encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. This gene is one of several located near the imprinted gene domain on chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2010]

CARS1 links:

CARS1-AS1 (HGNC:40125): (CARS1 antisense RNA 1)

CARS1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010881454).

BP6

Variant 11-3029392-G-A is Benign according to our data. Variant chr11-3029392-G-A is described in ClinVar as [Benign]. Clinvar id is 731546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00778 (1185/152350) while in subpopulation AMR AF= 0.0101 (154/15302). AF 95% confidence interval is 0.00936. There are 10 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARS1	NM_001014437.3 link	c.853C>T	p.Leu285Phe	missense_variant	8/23	ENST00000380525.9	NP_001014437.1	P49589-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9 link	c.853C>T	p.Leu285Phe	missense_variant	8/23	1	NM_001014437.3	ENSP00000369897.4		P49589-3

Frequencies

GnomAD3 genomes

AF:

0.00778

AC:

1185

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00998

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00758

AC:

1906

AN:

251400

Hom.:

AF XY:

0.00769

AC XY:

1045

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00972

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.0186

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00928

GnomAD4 exome

AF:

0.00945

AC:

13808

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00923

AC XY:

6709

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00358

Gnomad4 ASJ exome

AF:

0.00853

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.0177

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00888

GnomAD4 genome

AF:

0.00778

AC:

1185

AN:

152350

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

642

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0216

Gnomad4 NFE

AF:

0.00998

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00844

Hom.:

Bravo

AF:

0.00641

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00884

AC:

ExAC

AF:

0.00780

AC:

947

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00932

EpiControl

AF:

0.00759

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 26, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CARS1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.54

DANN

Benign

0.48

DEOGEN2

Benign

0.069

.;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.040

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.16

.;N;N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.53

N;N;N;.

REVEL

Benign

0.12

Sift

Benign

0.74

T;T;T;.

Sift4G

Benign

0.72

T;T;T;T

Polyphen

0.0, 0.0010

.;B;B;B

Vest4

0.16

MVP

0.21

MPC

0.26

ClinPred

0.0012

GERP RS

-3.0

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.018

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over